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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia
S Schnittger1, U Bacher, W Kern
1MLL Munich Leukemia Laboratory, Munich, Germany. susanne.schnittger@mll.com
Abstract:
High FLT3-ITD/wildtype (wt) load in FLT3-ITD-mutated AML has been associated with adverse impact on outcome in several studies. To clarify whether FLT3-ITD load as expressed as FLT3-ITD/wt ratio is also relevant in patients with NPM1 mutated AML, we assessed the FLT3-ITD mutation status and FLT3-ITD/wt ratio by fragment analysis in 638 NPM1mut AML (339 females; 299 males; 17.8-88.0 years), and analyzed its prognostic relevance in 355 patients. FLT3-ITD of various length and load were detected in 243/638 cases (38.1%). Median EFS (19.3 vs 9.7 months, P<0.001) and median 2-year survival rate (72.0 vs 52.7%, P=0.006) was better in FLT3wt (n=212 with available follow-up data) than FLT3-ITD (n=143). A higher FLT3-ITD/wt ratio as continuous variable was correlated with a shorter EFS (P=0.028). When patients were separated into subgroups according to the FLT3-ITD mutation load, only a FLT3-ITD/wt ratio 0.5 conferred an independent adverse impact on EFS and OS, and retained its prognostic significance also in multivariate analysis (P=0.009 for EFS, P=0.008 for OS). In conclusion, for risk estimation in NPM1 mutated AML not only the FLT3-ITD status, but also the FLT3-ITD load has to be taken into account. These data might contribute to clinical decision making in AML.
Insights
High FLT3-ITD load in NPM1-mutated AML significantly impacts patient outcomes. A FLT3-ITD/wildtype ratio above 0.5 indicates a worse prognosis, influencing clinical decisions.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- FLT3-ITD mutations are common in Acute Myeloid Leukemia (AML).
- High FLT3-ITD/wildtype (wt) load is linked to adverse outcomes in AML.
- The prognostic value of FLT3-ITD load in NPM1-mutated AML requires clarification.
Purpose of the Study:
- To investigate the prognostic relevance of FLT3-ITD/wt ratio in NPM1-mutated AML.
- To determine if FLT3-ITD load impacts event-free survival (EFS) and overall survival (OS).
Main Methods:
- Fragment analysis was used to assess FLT3-ITD mutation status and FLT3-ITD/wt ratio.
- 638 patients with NPM1-mutated AML were analyzed for mutation status.
- Prognostic relevance was analyzed in 355 patients with available follow-up data.
Main Results:
- FLT3-ITD mutations were detected in 38.1% of patients.
- Patients with FLT3-ITD had significantly shorter EFS and lower 2-year survival rates compared to FLT3wt.
- A FLT3-ITD/wt ratio >0.5 was an independent adverse prognostic factor for EFS and OS, confirmed by multivariate analysis.
Conclusions:
- FLT3-ITD mutation status and load are crucial for risk stratification in NPM1-mutated AML.
- The FLT3-ITD/wt ratio provides independent prognostic information.
- These findings can aid clinical decision-making for AML patients.
